Associations Of Plasma Metal Concentrations With The Risks Of All-cause And Cardiovascular Disease Mortality In China

Objective:Exposure to metal/metalloid from both the natural environment and anthropogenic activities enter the human body through multiple routes,and exert a complex influence on human health.However,prospective studies regarding the associations between exposure to multiple metals/metalloids and mortality are limited.Therefore,we aimed to prospectively evaluate the associations of multiple metal/metalloids exposures with all-cause and cardiovascular disease（CVD）mortality based on the Dongfeng-Tongji cohort.Methods:A total of 6155 participants within three nested case-control studies in the Dongfeng-Tongji cohort were included in the current study,which were followed for mortality until December 31,2018.We measured baseline plasma concentrations of 23metals and utilized Cox regression models to calculate the hazard ratios（HRs）for all-cause and CVD mortality associated with plasma metal exposure.We proposed plasma metal score through summing each metal concentration weighted by the regression coefficients with all-cause mortality,and comprehensively assess the relations between simultaneous exposure to multiple metals and all-cause and CVD mortality.Results:During the follow-up（mean duration,9.8 years）,we ascertained 876 deaths,including 416 deaths of CVD.In the multiple-metals model,after adjustment of potential confounders,plasma copper（Cu）,molybdenum（Mo）,and vanadium（V）were positively associated with all-cause mortality,whereas manganese（Mn）,selenium（Se）,and thallium（Tl）were negatively associated with all-cause mortality,with adjusted HRs（95%CI）of the fourth quartiles were 1.73(1.42-2.11,P _trend<0.001)for Cu,1.33(1.09-1.63,P _trend=0.005)for Mo,1.43(1.16-1.77,P _trend<0.001)for V,0.74(0.58-0.94,P _trend=0.005)for Mn,0.68(0.56-0.83,P _trend<0.001)for Se,and 0.74(0.59-0.92,P _trend=0.002)for Tl,respectively.Positive associations were observed between plasma Cu,Mo,and V levels and CVD mortality,whereas plasma Se and Tl levels showed negative associations with CVD mortality in the multiple-metals model.Compared with the first quartiles,the HRs（95%CI）of fourth quartiles were 1.94(1.45-2.58,P _trend<0.001)for Cu,1.72（1.26-2.35,P trend<0.001）for Mo,1.81（1.32-2.47,P trend<0.001）for V,0.67（0.50-0.89,P trend=0.003）for Se,and 0.58（0.41-0.81,P trend<0.001）for Tl,respectively.The multiple-metals model selected 6 metals（Cu,Mo,V,Mn,Se and Tl）to establish plasma metal scores.After adjusted for established risk factors,the plasma metal score was significantly associated with higher risks of all-cause and CVD death in dose-response fashions.When compared with the first quartiles of plasma metal score,the HRs（95%CI）of fourth quartiles were 2.23(1.82-2.74;P _trend<0.001)for all-cause mortality and 3.62(2.63-4.98;P _trend<0.001)for CVD mortality.Conclusions:Our findings suggested that elevated plasma concentrations of Cu,Mo,and V were associated with higher risks of all-cause and CVD mortality,while elevated concentrations of Mn,Se,and Tl were associated with lower risks of all-cause mortality.Additionally,higher concentrations of Se and Tl were associated with lower risk of CVD mortality.The study indicated that several plasma metals/metalloids were key determinants and predictors of all-cause and CVD mortality in the Chinese population.Our findings highlighted the importance to comprehensively assess and monitor multiple metals/metalloids exposures.